In encapsulated cell therapy, xenogenic or allogenic cells are isolated from the host's immune system by being surrounded in a semi-permeable membrane prior to implantation within the host. The semi-permeable membrane is relatively impermeable to large molecules, such as components of the host's immune system, but is permeable to small molecules. Thus, the semi-permeable membrane allows the implanted cells to receive nutrients necessary for viability and allows metabolic waste to be removed. The membrane also allows therapeutic molecules produced by the implanted cells to diffuse to host cells. For example, endogenous proteins or those cloned into the cell are delivered to the host. The use of an immuno-protective, semi-permeable membrane now allows transplantation of encapsulated cells from one species into a host from a different species without the risk of immune rejection or use of immunosuppressive drugs. Applications of encapsulated cell therapy include, for example, treatment for diabetes, haemophilia, anemia, .beta.-thalassemia, Parkinson's disease, and amyotropic lateral sclerosis.
The use of biologically compatible polymeric materials in construction of an encapsulation device is critical to a successful cell encapsulation therapy. Important components of the encapsulation device include the surrounding semi-permeable membrane and the internal cell-supporting matrix or scaffold. The scaffold defines the microenvironment for the encapsulated cells and keeps the cells well distributed within the intracapsular compartment. The optimal internal scaffold for a particular cell encapsulation device is highly dependent on the cell type. For example, while adherent cells often prefer a solid surface on which to lie, suspension cells may prefer a hydrophilic lightly cross-linked hydrogel as a matrix material.
In the absence of a scaffold, adherent cells aggregate to form clusters. When the clusters grow too large, they typically develop a central necrotic core. Dying cells accumulate around the core and, upon lysing, release factors detrimental to the health of neighboring cells. The lysed cell fragments are also transported to the host environment, there eliciting an antigenic response.
Several types of prior art devices have attempted to solve these problems, meeting with mixed results. For example, the prior art includes the use of bonded fiber structures for cell implantation (U.S. Pat. No. 5,512,600) and the use of biodegradable polymers as scaffolds for organ regeneration such as, for example, liver, pancreas, and cartilage. The use of biodegradable polymers for use as scaffolds in organ regeneration is reviewed by Cima et al., BIOTECH. BIOENG. 38: 145-58 (1991). In these prior art works, biodegradable fiber tassels and fiber-based felts (i.e., non-woven materials) were used as scaffolds for transplanted cells. One drawback to the use of biodegradable polymers, particularly polymers of poly(lactic acid) PLA, poly(lactic-coglycolic acid) PLGA, poly(glycolic acid) PGA, and their equivalents, is that upon degradation, they release lactic and/or glycolic acid, which are toxic to surrounding tissue. As the polymers degrade, they break down to first low molecular weight oligomers and then to the acids, causing a rapid increase in acid released into the surrounding tissue. This rise in acid concentration in vivo in the local environment of the implant can induce an inflammatory response or tissue necrosis.
Foam scaffolds have also been used in the art to provide surfaces onto which transplanted cells may adhere. Foam scaffolds, however, have random flat surfaces and do not provide a linear template for reorganization. Some cell types prefer such a template for organization into physiological three-dimensional orientation.
Prior art also includes woven mesh tubes used as vascular grafts. Although cells may be seeded onto these woven tubes for improved biocompatibility, these tubes function primarily as vascular conduits and not cell scaffolds.
Thus, a need exists in the art for a non-degradable scaffold or framework system to provide an ordered linear environment for cells which prefer such an environment to grow and proliferate within cell encapsulation devices.